Biomedical Engineering and Bioengineering Commons^™

Method Validation Of Functional Magnetic Resonance Imaging And Electrophysiological Recording To Investigate Mechanisms Of Vagus Nerve, Christina L. Hendren, Jiayue Cao, Zhongming Liu

The Summer Undergraduate Research Fellowship (SURF) Symposium

Vagus nerve stimulation (VNS) is used clinically to treat epilepsy and depression, but its mechanism of action is unknown. Useful techniques to study this are functional magnetic resonance imaging (fMRI) and the local field potential (LFP). fMRI relies on oxygen use in the brain to show areas where neurons are active. The LFP is an electrical signal created by neuron action potentials and other current moving across cell membranes. The most information can be gained when the two methods are used simultaneously, however, this is difficult to do. This study seeks to validate the technique of fMRI-LFP as applied to …

Flow Chamber For Confocal Tracking Of Particles In Bone, Brennan Flannery, Russell Main, Xiaoyu Xu

The Summer Undergraduate Research Fellowship (SURF) Symposium

Interstitial fluid flow in the lacunar-canalicular system (LCS) of bone is recognized as a potential regulator of bone remodeling. Movement of fluid across bone cells called osteocytes regulates gene expression that leads to either bone formation or resorption. Interstitial fluid moves in response to bone loading during daily activity, and bone growth occurs to compensate for these loads, affecting bone shape and strength. While interstitial fluid flow is thoroughly studied using computational models, there is a critical need to study flow in real bone samples with imaging techniques. Flow velocities determined from imaging will be more accurate than computational models …

Neuroimaging Biomarkers Of Mtor Inhibition On Vascular And Metabolic Functions In Aging Brain And Alzheimer’S Disease, Jennifer Lee, Lucille M. Yanckello, David Ma, Jared D. Hoffman, Ishita Parikh, Scott Thalman, Bjoern Bauer, Anika M. S. Hartz, Fahmeed Hyder, Ai-Ling Lin

Pharmacology and Nutritional Sciences Faculty Publications

The mechanistic target of rapamycin (mTOR) is a nutrient sensor of eukaryotic cells. Inhibition of mechanistic mTOR signaling can increase life and health span in various species via interventions that include rapamycin and caloric restriction (CR). In the central nervous system, mTOR inhibition demonstrates neuroprotective patterns in aging and Alzheimer’s disease (AD) by preserving mitochondrial function and reducing amyloid beta retention. However, the effects of mTOR inhibition for in vivo brain physiology remain largely unknown. Here, we review recent findings of in vivo metabolic and vascular measures using non-invasive, multimodal neuroimaging methods in rodent models for brain aging and AD. …

Developing Droplet Based 3d Cell Culture Methods To Enable Investigations Of The Chemical Tumor Microenvironment, Jacqueline Alexandria De Lora

Biomedical Sciences ETDs

Adaptation of cancer cells to changes in the biochemical microenvironment in an expanding tumor mass is a crucial aspect of malignant progression, tumor metabolism, and drug efficacy. In vitro, it is challenging to mimic the evolution of biochemical gradients and the cellular heterogeneity that characterizes cancer tissues found in vivo. It is well accepted that more realistic and controllable in vitro 3D model systems are required to improve the overall cancer research paradigm and thus improve on the translation of results, but multidisciplinary approaches are needed for these advances. This work develops such approaches and demonstrates that new droplet-based cell-encapsulation …

Super‐Resolution Imaging Of Amyloid Structures Over Extended Times By Using Transient Binding Of Single Thioflavin T Molecules, Kevin Spehar, Tianben Ding, Yuanzi Sun, Niraja Kedia, Jin Lu, George R. Nahass, Matthew D. Lew, Jan Bieschke

Electrical & Systems Engineering Publications and Presentations

Oligomeric amyloid structures are crucial therapeutic targets in Alzheimer's and other amyloid diseases. However, these oligomers are too small to be resolved by standard light microscopy. We have developed a simple and versatile tool to image amyloid structures by using thioflavin T without the need for covalent labeling or immunostaining. The dynamic binding of single dye molecules generates photon bursts that are used for fluorophore localization on a nanometer scale. Thus, photobleaching cannot degrade image quality, allowing for extended observation times. Super‐resolution transient amyloid binding microscopy promises to directly image native amyloid by using standard probes and record amyloid dynamics …

Weighting Function Effects In A Direct Regularization Method For Image-Guided Near-Infrared Spectral Tomography Of Breast Cancer., Jinchao Feng, Shudong Jiang, Brian W. Pogue, Keith Paulsen

Dartmouth Scholarship

Structural image-guided near-infrared spectral tomography (NIRST) has been developed as a way to use diffuse NIR spectroscopy within the context of image-guided quantification of tissue spectral features. A direct regularization imaging (DRI) method for NIRST has the value of not requiring any image segmentation. Here, we present a comprehensive investigational study to analyze the impact of the weighting function implied when weighting the recovery of optical coefficients in DRI based NIRST. This was done using simulations, phantom and clinical patient exam data. Simulations where the true object is known indicate that changes to this weighting function can vary the contrast …

Correcting For Targeted And Control Agent Signal Differences In Paired-Agent Molecular Imaging Of Cancer Cell-Surface Receptors, Negar Sadeghipour, Scott C. Davis, Kenneth M. Tichauer

Dartmouth Scholarship

Paired-agent kinetic modeling protocols provide one means of estimating cancer cell-surface receptors with in vivo molecular imaging. The protocols employ the coadministration of a control imaging agent with one or more targeted imaging agent to account for the nonspecific uptake and retention of the targeted agent. These methods require the targeted and control agent data be converted to equivalent units of concentration, typically requiring specialized equipment and calibration, and/or complex algorithms that raise the barrier to adoption. This work evaluates a kinetic model capable of correcting for targeted and control agent signal differences. This approach was compared with an existing …

Medical Perspective Articles To Stimulate The Field For Needs-Finding, Brian W. Pogue

Dartmouth Scholarship

This editorial by the journal's Editor in Chief, Brian Pogue, explains the need for a new type of paper.

New Algorithms For Compressed Sensing Of Mri: Wtwts, Dwts, Wdwts, Srivarna Settisara Janney

Master of Science in Computer Science Theses

Magnetic resonance imaging (MRI) is one of the most accurate imaging techniques that can be used to detect several diseases, where other imaging methodologies fail. MRI data takes a longer time to capture. This is a pain taking process for the patients to remain still while the data is being captured. This is also hard for the doctor as well because if the images are not captured correctly then it will lead to wrong diagnoses of illness that might put the patients lives in danger. Since long scanning time is one of most serious drawback of the MRI modality, reducing …

Submandibular Mechanical Stimulation Of Upper Airway Muscles To Treat Obstructive Sleep Apnea, Ferhat Erdogan

Dissertations

The extrinsic tongue muscles are activated in coordination with pharyngeal muscles to keep a patent airway during respiration in wakefulness and sleep. The activity of genioglossus, the primary tongue-protruding muscle playing an important role in this coordination, is known to be modulated by several reflex pathways mediated through the mechanoreceptors of the upper airways. The main objective is to investigate the effectiveness of activating these reflex pathways with mechanical stimulations, for the long-term goal of improving the upper airway patency during disordered breathing in sleep. The genioglossus response is examined during mandibular and sub-mandibular mechanical stimulations in healthy subjects during …

Developing Wavefront Shaping Techniques For Focusing Through Highly Dynamic Scattering Media, Ashton Hemphill

McKelvey School of Engineering Graduate Student Theses & Dissertations

One of the prime limiting factors of optical imaging in biological applications is the diffusion of light by tissue, which prevents focusing at depths greater than the optical diffusion limit of ~1 mm in soft tissue. This greatly restricts the utility of optical diagnostic and therapeutic techniques, such as optogenetics, microsurgery, optical tweezing, and phototherapy of deep tissue, which require focused light in order to function. Wavefront shaping extends the depth at which optical focusing may be achieved by compensating for phase distortions induced by scattering, allowing for focusing through constructive interference.

However, due to physiological motion, scattering of light …

Fluorescence Guided Tumor Imaging: Foundations For Translational Applications, Jessica P. Miller

McKelvey School of Engineering Graduate Student Theses & Dissertations

Optical imaging for medical applications is a growing field, and it has the potential to improve medical outcomes through its increased sensitivity and specificity, lower cost, and small instrumentation footprint as compared to other imaging modalities. The method holds great promise, ranging from direct clinical use as a diagnostic or therapeutic tool, to pre-clinical applications for increased understanding of pathology. Additionally, optical imaging uses non-ionizing radiation which is safe for patients, so it can be used for repeated imaging procedures to monitor therapy, guide treatment, and provide real-time feedback. The versatile features of fluorescence-based optical imaging make it suited for …

Developing Photoacoustic Tomography Devices For Translational Medicine And Basic Science Research, Tsz Wai Wong

McKelvey School of Engineering Graduate Student Theses & Dissertations

Photoacoustic (PA) tomography (PAT) provides volumetric images of biological tissue with scalable spatial resolutions and imaging depths, while preserving the same imaging contrast—optical absorption. Taking the advantage of its 100% sensitivity to optical absorption, PAT has been widely applied in structural, functional, and molecular imaging, with both endogenous and exogenous contrasts, at superior depths than pure optical methods. Intuitively, hemoglobin has been the most commonly studied biomolecule in PAT due to its strong absorption in the visible wavelength regime.

One of the main focuses of this dissertation is to investigate an underexplored wavelength regime—ultraviolet (UV), which allows us to image …

A Study Of Acoustically Activated Nanodroplets, Songita Choudhury

Theses & Dissertations

Current treatment of acute myocardial infarction (AMI), which is the main pathophysiological event leading to death in the United States, has advanced considerably with the introduction of emergent percutaneous interventions, but there remains an urgent need for novel techniques to rapidly and accurately detect infarcted or ischemic tissue that results from AMI. Ultrasound contrast agents, also known as microbubbles (MB), have become commonplace in echocardiography. However, MBs are purely intravascular tracers and unable to cross endothelial barriers due to size. The limitations of MBs, namely size and short circulation times within the human body, led to the development of phase-change …

Quantification Of Tumor-Associated Macrophages Following Immunomodulation Therapy In A Murine Allograft Model Of Colorectal Carcinoma, Caroline Spainhour

Biomedical Engineering Undergraduate Honors Theses

Colorectal Carcinoma (CRC) is one of the deadliest cancers in the world, with 150,000 new cases annually in the United States. Traditional treatments include chemotherapy and invasive surgery; however, research has shown that only 25% of patients that undergo traditional treatment have a positive result. Immunotherapy is an emerging form of cancer treatment that utilizes the patients’immune system to fight cancer cells by targeting inflammation, which plays a large role in the proliferation and metastasis of cancer cells.

Tumor-associated macrophages (TAMs) are immune cells that affect the inflammatory microenvironment of tumors. TAMs are M1 in the early stages of tumors, …

Experimental And Model-Based Terahertz Imaging And Spectroscopy For Mice, Human, And Phantom Breast Cancer Tissues, Tyler Bowman

Graduate Theses and Dissertations

The goal of this work is to investigate terahertz technology for assessing the surgical margins of breast tumors through electromagnetic modeling and terahertz experiments. The measurements were conducted using a pulsed terahertz system that provides time and frequency domain signals. Three types of breast tissues were investigated in this work. The first was formalin-fixed, paraffin-embedded tissues from human infiltrating ductal and lobular carcinomas. The second was human tumors excised within 24-hours of lumpectomy or mastectomy surgeries. The third was xenograft and transgenic mice breast cancer tumors grown in a controlled laboratory environment to achieve more data for statistical analysis.

Experimental …

Comparison Of Varying Tissue Freezing Methods On Murine Colonic Tissue, James Hughes

Biomedical Engineering Undergraduate Honors Theses

Histology often requires a tissue specimen to be embedded so that it may be sectioned, stained, and mounted on a microscope slide for viewing. One common method of tissue embedding for rapid histology is freezing, since freezing allows tissue to be stored without the need for fixing. Frozen tissue is often embedded in a medium such as Optimal Cutting Temperature (OCT) compound so that it can be sectioned using a cryostat. However, factors such as ice-crystal formation during the freezing process can cause damage to the tissue. As such, the protocol used to freeze the tissue can affect the quality …

Modeling Eeg And Tdcs In Scirun Software Packages, Aiden Keene, Aiden Thomas Keene

Senior Honors Projects

Never before has there been a greater emphasis on improving the shortcomings of treating mental health conditions. Our generation has more knowledge about technological practices with the potential to monitor and treat mental health symptoms than that of any generation before us. A breakthrough in this field made by CREmedical is called Tripolar Concentric Ring Electrodes (TCRE’s), which can measure signals from the brain more accurately than conventional electrodes. At CREmedical, TCREs are being used to study differences in electrical activity in the brain so as to identify abnormalities, and monitor responses to stimulation therapies. This semester I had the …

Extraction And Analysis Of Vector Flow Imaging Data In A Pediatric Population, Bailey Stinnett

Biomedical Engineering Undergraduate Honors Theses

Vector flow imaging (VFI) is a new ultrasound technology that provides real time, angle-independent visualization of flow velocities in the heart and great vessels. Thus far, VFI has been used for superficial applications due to the limited penetration depth of available transducer probes; however, this depth in smaller pediatric patients enables adequate aortic views. In this project, VFI was used to study pediatric aortic stenosis (PAS)—a congenital heart defect that results in the narrowing of the aorta and/or aortic valve. The decision to refer PAS patients for surgical or catheter-based intervention is initially based on Doppler ultrasound. VFI is potentially …

Renal Granulomatosis Post Intravesical Bacillus Calmette-Guerin Therapy For Non-Muscle-Invasive Bladder Cancer, Karen Tran-Harding, Rashmi T. Nair, Halemane S. Ganesh

Radiology Faculty Publications

Intravesical Bacillus Calmette–Guerin (BCG) immunotherapy is a proven, effective treatment for intermediate- and high-risk non-muscle-invasive bladder cancer. Minor side effects are common and expected but systemic effects can occur in < 5% of treated patients. We present a rare case of a 49-year-old male that presented with fever and chills after 3 weeks of intravesical BCG therapy post transurethral resection of bladder tumor. New renal lesions were present on contrast-enhanced computed tomography scan which was histologically proven to be necrotizing renal granulomatosis.

An Area Based Fan Beam Projection Model, Richard E. Steele, Jiehua Zhu

Honors College Theses

Area based projection models for computed tomography mitigate raw data errors by treating X-Rays as beams, whereas traditional line based projection models treat an X-Ray like a line, thus generating significant error. In an existing area based fan beam projection model, a rotation matrix, Q, simulates the rotation of the emitter detector pair to reduce computational load, but this introduces approximations by using an approximated rotation matrix. We eliminate approximations by deriving an exact formula for the entries of Q. Using a rotation of axes and by considering the neighboring cells' contributions to the area, the result has formulations for …

Characterization Of Computed Tomography Radiomic Features Using Texture Phantoms, Muhammad Shafiq Ul Hassan

USF Tampa Graduate Theses and Dissertations

Radiomics treats images as quantitative data and promises to improve cancer prediction in radiology and therapy response assessment in radiation oncology. However, there are a number of fundamental problems that need to be solved in order to potentially apply radiomic features in clinic. The first basic step in computed tomography (CT) radiomic analysis is the acquisition of images using selectable image acquisition and reconstruction parameters. Radiomic features have shown large variability due to variation of these parameters. Therefore, it is important to develop methods to address these variability issues in radiomic features due to each CT parameter. To this end, …

Optimization Of Microfluidic Chip Fabrication Via Femtosecond Laser Ablation, Kenneth Aycock

Senior Theses

Microfluidic devices have become staple tools in biomedical research and have a promising future as low cost, point-of-care (POC) diagnostic devices. Despite the advancements in microfluidic device technology, the manipulation and fabrication of these systems can be tedious and expensive. Repeatable techniques in which computer-aided designs are translated into microfluidic systems in a matter of minutes are highly desirable both for researchers and manufacturers. Laser ablation of tape substrates has shown promise in producing cost-effective, rapidly manipulable devices, but the work done thus far has utilized continuous wave lasers that perform suboptimally due to the relatively short wavelengths used and …

Tracing Actin Filament Bundles In Three-Dimensional Electron Tomography Density Maps Of Hair Cell Stereocilia, Salim Sazzed, Junha Song, Julio Kovacs, Willi Wriggers, Manfred Auer, Jing He

Computer Science Faculty Publications

Cryo-electron tomography (cryo-ET) is a powerful method of visualizing the three-dimensional organization of supramolecular complexes, such as the cytoskeleton, in their native cell and tissue contexts. Due to its minimal electron dose and reconstruction artifacts arising from the missing wedge during data collection, cryo-ET typically results in noisy density maps that display anisotropic XY versus Z resolution. Molecular crowding further exacerbates the challenge of automatically detecting supramolecular complexes, such as the actin bundle in hair cell stereocilia. Stereocilia are pivotal to the mechanoelectrical transduction process in inner ear sensory epithelial hair cells. Given the complexity and dense arrangement of actin …

Radiotherapy-Induced Cherenkov Luminescence Imaging In A Human Body Phantom, Syed Rakin Ahmed, Mengyu Jia, Petr Bruza, Sergei A. Vinogradov, Shudong Jiang, David J. Gladstone, Lesley A. Jarvis, Brian W. Pogue

Dartmouth Scholarship

Radiation therapy produces Cherenkov optical emission in tissue, and this light can be utilized to activate molecular probes. The feasibility of sensing luminescence from a tissue molecular oxygen sensor from within a human body phantom was examined using the geometry of the axillary lymph node region. Detection of regions down to 30-mm deep was feasible with submillimeter spatial resolution with the total quantity of the phosphorescent sensor PtG4 near 1 nanomole. Radiation sheet scanning in an epi-illumination geometry provided optimal coverage, and maximum intensity projection images provided illustration of the concept. This work provides the preliminary information needed to attempt …

P-42 Using The Raspberry Pi For Ecl Reaction Analysis, Jonathan Swerdlow

Honors Scholars & Undergraduate Research Poster Symposium Programs

Using a Raspberry Pi and its camera module, we developed an affordable and easily available system for photographing and analyzing electrochemiluminescent (ECL) reactions. These reactions can be represented as a function of average light intensity over time, allowing for a future program to determine the concentration of certain reactants. Such ECL reactions will be useful in the diagnosis of medical conditions such as cancer without the need for expensive equipment or laboratories. The proposed system will make certain diagnoses easy and available to people across the globe and will likely require only a small blood sample. It will also be …

Optimal Wavelength Selection For Optical Spectroscopy Of Hemoglobin And Water Within A Simulated Light-Scattering Tissue, Mikael Marois, Stephen L. Jacques, Keith D. Paulsen

Dartmouth Scholarship

An algorithm that selects optimal wavelengths for spectral fitting of diffuse light reflectance spectra using a nonnegative least squares method is presented. Oxyhemoglobin, deoxyhemoglobin, and water are considered representative absorbers, but the approach is not constrained or limited by absorber selection provided native basis spectra are available. The method removes wavelengths iteratively from a scattering-modulated absorption matrix by maximizing the product of its singular values and offers considerable improvements over previously published wavelength selection schemes. Resulting wavelength selections are valid for a broad range of optical properties and yield lower RMS errors than other wavelength combinations. The method is easily …

Biomedical Optics Scientific Community, Brian W. Pogue

Dartmouth Scholarship

The new Editor-in-Chief, Brian Pogue, gives an overview of the biomedical optics community.

The Effects Of Emerging Technology On Healthcare And The Difficulties Of Integration, Skyler J. Pavlish-Carpenter

Honors Undergraduate Theses

Background: Disruptive technology describes technology that is significantly more advanced than previous iterations, such as: 3D printing, genetic manipulation, stem cell research, innovative surgical procedures, and computer-based charting software. These technologies often require extensive overhauls to implement into older systems and must overcome many difficult financial and societal complications before they can be widely used. In a field like healthcare that makes frequent advancements, these difficulties can mean that the technology will not be utilized to its full potential or implemented at all.

Objective: To determine the inhibiting factors that prevent disruptive technology from being implemented in conventional healthcare.

Methods: …

Early Emerging Pathogen Detection, Mackenzie Wangenstein

Maseeh Summer Undergraduate Research Experience

A supervised learning technique was employed to identify emerging pathogen species. Portland State University has partnered with the University of New Mexico to take encodings of unknown pathogen molecular structures to determine emerging species.